Methods and apparatus for delivering aerosolized medication

ABSTRACT

A metered dose inhaler (10) for use with a pressurized aerosol canister (18) includes a housing (12) defining a conduit (16) with a mouthpiece (56), and an actuator (26) with a nozzle discharge orifice (30) arranged to discharge aerosol into the conduit. An air tube (34) is arranged within the conduit with an inlet (38) of the air tube formed in the conduit wall (74) and an outlet (36) of the air tube in opposing relationship with the nozzle orifice. Inhalation through the mouthpiece causes air to be drawn into the inlet and flow out of the outlet of the air tube to form an air jet which impinges on an oppositely moving aerosol plume from the orifice. Automatic actuation of the canister responsive to the patient&#39;s inhalation is achieved by a canister trigger (154) connected to a movable piston assembly (132) forming a wall of a variable-volume chamber (162) in fluid communication with a venturi (184) in the air tube. Air drawn through the venturi by the user&#39;s breath causes evacuation of air from the chamber, thereby moving the piston assembly and trigger to cause actuation of the canister.

This application is a continuation of U.S. application Ser. No.08/954,352, filed Oct. 17, 1997, now U.S. Pat. No. 5,954,047.

FIELD OF THE INVENTION

The present invention relates to method and apparatus for delivering adose of aerosolized medication for inhalation by a patient into thelungs.

BACKGROUND OF THE INVENTION

Aerosols are increasingly being used for delivering medication fortherapeutic treatment of the lungs. For example, in the treatment ofasthma, inhalers are commonly used for delivering bronchodilators suchas β₂ agonists and anti-inflammatory agents such as corticosteroids. Twotypes of inhalers are in common use, metered dose inhalers (MDIs) anddry powder inhalers (DPIs). Both types have as their object the deliveryof medication, which is typically in the form of a solid particulate orpowder, into the airways of the lungs at the location of the conditionbeing treated.

In the MDI device, the medication is provided by the pharmaceuticalmanufacturer in a pressurized aerosol canister, with the medicationbeing suspended or dissolved in a liquid propellant such as achlorofluorcarbon (CFC) or hydrofluroralkane (HFA). The canisterincludes a metering valve having a hollow discharge stem which can bedepressed inward into the canister to discharge a metered volume ofpropellant-medication mixture in the form of an aerosol comprising finedroplets of propellant in which particles of the medication aresuspended or dissolved. A typical MDI for use with such a canisterincludes a housing having an actuator and nozzle. The canister isinserted into the housing with the hollow discharge stem of the canisterbeing received in a bore in the actuator. Depressing the closed end ofthe canister causes the stem to be pushed inward into the canister sothat a metered volume of medication is discharged through the nozzle.The housing further defines a flowpath in fluid communication with thenozzle, the flowpath having an outlet at a mouthpiece portion of thehousing, such that the aerosolized medication may be inhaled after itexists the mouthpiece portion. The patient either inserts the mouthpieceinto the mouth with the lips closed around the mouthpiece, or holds themouthpiece at a slight distance away from an open mouth. The patientthen depresses the canister to discharge the medication, andsimultaneously inhales.

Existing MDIs suffer from a number of significant disadvantages. Oneproblem with existing MDIs is poor delivery efficiency of themedication. It has been estimated that on average, with existing MDIs,only about 10 percent of the medication does which is dispensed from thecanister actually reaches the lungs where it can achieve the intendedresult.

Poor delivery efficiency is caused by a number of factors. One of theseis incomplete evaporation of propellant, resulting in a large portion ofthe metered does being delivered in a form which cannot be inhaled intothe lungs. For effective delivery of aerosolized medication to theairways of the lungs, it is desirable that most of the particles whichare inspired be less than about 10 microns (one micron=one-thousandth ofa millimeter) in size, and preferably between about 1 micron and 5microns. Incomplete evaporation of propellant at the outlet of themouthpiece results in a substantial fraction of the metered dose beingdelivered in the form of relatively large liquid droplets instead offine dry particles and/or vapor. Such droplets cannot be inspired, butrather tend to impact the inside of the mouth and at the back of thepatient's throat, with the result that much of the medication isswallowed. The local concentration of medication in the mouth and throatcan cause local immuno-suppression response, as well as development offungal infections in the case of corticosteroids. Additionally,swallowing β₂ agonists causes relaxation of the smooth muscles of thegastrointestinal tract, which decreases contractility and activity ofthe stomach. Further, the wasted medication has been estimated to costU.S. patients about $750 million per year.

Another factor contributing to the problem of poor delivery efficiencyis high linear velocity of the aerosol as it exits the mouthpiece, whichtends to lead to impaction of the aerosol in the mouth and throat.Ideally, the velocity of the aerosol should match the velocity of thepatient's inspired breath so that the particles are entrained in thebreath and carried into the lungs. With many existing MDIs, the exitvelocity of the aerosol substantially exceeds the velocity of thepatient's breath. The high-velocity plume strikes the back of thethroat, causing impaction and sticking.

Yet another factor contributing to the poor delivery efficiency ofexisting MDIs is excessive length of the plume or bolus of aerosolexiting the device. In existing MDIs, this length typically exceeds 25centimeters, which makes it difficult for the patient to inhale theentire bolus.

In an effort to decrease plume velocity, some MDI designers have addedtubular spacers between the aerosol nozzle and the mouthpiece. Althoughspacers improve delivery efficiency, most of the drug which isdischarged from the nozzle impacts and sticks on inner surfaces of thespacer, and is therefore unavailable for inhalation by the user. Thus,MDIs wit spacers still suffer from unacceptably low deliveryefficiencies.

Furthermore, although dry powder inhalers inherently avoid some of theaforementioned problems of MDIs, such as excessive aerosol velocity,DPIs still suffer from the problem of impaction and sticking ofmedication on the inner surfaces of the devices, particularly undercertain environment conditions such as high relative humidity, whichtends to cause particle aggregation.

Another problem with existing MDIs is the difficulty patients have incoordinating their inhalation with the discharge of the aerosol. Inmanually operated MDIs, patients frequently inhale too early or too lateto effectively inspire the medicaiton. Although a number ofbreath-actuated MDIs have been devised to address this problem, most ofthese devices cause discharge at the very onset of the patient'sinspiratory effort. Depending on the lung condition being treated andits location, it may often be more desirable for he medication to bedischarged near the peak of the patient's inhalation rather than thebeginning. Further, it may be desirable to be able to selectively varythe point in the patient's inhalation at which medication is dischargedin order to tailor the location of drug delivery to the condition beingtreated. These advantages are not possible with existing MDIs.

Accordingly, it has been an object of the present invention to provide amethod and apparatus for delivering an aerosolized medication in whichthe respirable fraction of the metered dose (i.e., fraction in he formof dry particles of the optimum size) is maximized at the exit of theapparatus.

It has been a further object of the present invention to provide amethod and apparatus for delivering an aerosolized medication in whichthe linear velocity of the aerosol at the exit of the apparatusapproximately matches the velocity of he patient's inspired breath.

It has been another object of the invention to maximize dispersion andmixing of the drug particles in the bolus of an aerosol within aninhaler apparatus.

It has been a still further object of the present invention to provide amethod and apparatus for delivering an aerosolized medication in whichthe length of the bolus of aerosolized medication which exits theapparatus is as short as possible.

A further object of the invention has been to provide a method andapparatus for maximizing the evaporation of liquid propellant in aninhaler.

Still another object of the invention has been to provide a method andapparatus for delivering an aerosolized medication in which impactionand sticking of medication on the inner walls of the apparatus isminimized.

It has been another object of the present invention to provide a methodand apparatus for delivering an aerosolized medication in which thedischarge of medication is synchronized with the patient's inspiredbreath, and in which the timing of the discharge in relation to thepatient's breath can be selectively varied.

SUMMARY OF THE INVENTION

The above and other objects of the invention are achieved by the methodsand apparatus of the invention in which flow control techniques anddevices are used to promote mixing of the propellant-medication mixturewith air to increase evaporation of propellant, to slow down the aerosolplume before it reaches the exit of the apparatus, and to reduce theimpaction of aerosol on the inner walls of the apparatus. The inventionalso provides an apparatus and method for synchronizing the actuation ofthe canister with the patient's inspiratory effort exerted on themouthpiece of the apparatus.

More specifically, the invention provides a metered does inhalerapparatus including a housing adapted to support a pressurized canister,the housing having an actuator and nozzle assembly with a bore adaptedto receive the hollow outlet stem of the canister, the housing furtherincluding a generally tubular conduit having an open end forming amouthpiece adapted to be inserted into the mouth of a user, a nozzledischarge orifice of the actuator and nozzle assembly being positionedto direct a plume of aerosolized medication into the conduit; and an airtube supported within the conduit and having an air tube outlet arrangedopposite the nozzle discharge orifice and an air tube inlet in fluidcommunication with ambient air outside the conduit, the air tube beingoriented so that air flowing out of the air tube outlet is directed soas to impinge on a plume of aerosolized medication discharged from thecanister through the nozzle discharge orifice. Thus, an inspiratoryeffort exerted on the mouthpiece causes air to flow into the air tubeinlet and out the air tube outlet to impinge on the plume and therebyenhance dispersion and mixing of the medication within the conduit. Theair jet from the air tube also causes the plume to slow down so that thevelocity of the aerosol exiting the device approximately matches thevelocity of a patient's inspired breath. Slowing down the plume alsoincreases the residence time of the aerosol within the apparatus andleads to a shorter bolus to be inhaled. The increased mixing andresidence time promote more complete evaporation of propellant at theexit of the mouthpiece.

In one embodiment of the invention, the apparatus is configured so thatthe nozzle discharge orifice directs a plume toward the open end of themouthpiece. The air tube is arranged to direct an air jet away from theopen end of the mouthpiece so as to impinge on the plume. The air tubeis supported within the conduit by one or more hollow spokes connectedto the wall of the conduit, with the hollow passage of each spoke beingconnected atone end to a corresponding passage through the conduit wallto ambient air outside the conduit and at the other end to the inlet ofthe air tube. When the patient inhales on the open end of themouthpiece, air is drawn into the air tube to cause an air jet to exitthe air tube. Once this air jet has been established, the canister isactuated to discharge a plume of aerosol toward the air jet. The plumeand air jet meet, causing mixing and deceleration of the plume.

In another embodiment of the invention, the nozzle is positioned todirect a plume away from the open end of the mouthpiece toward the farend of the conduit, which end is substantially closed by an end wall.The air tube is mounted on the end wall, with the inlet of the air tubeconnected to a passage through the end wall to ambient air outside theconduit. Inhalation by a patient on the open end causes air to be drawnthrough the air tube in a direction toward the patient's mouth. Once theair jet from the air tube has been established, the canister isactivated to direct a plume toward the closed end of the conduit. Theair jet and plume meet, causing mixing and deceleration of the plume.The plume must reverse direction before exiting the mouthpiece, so thatthe same length of conduit is used twice, thereby further increasingresidence time of the aerosol within the device.

To reduce impaction and sticking of medication on the inner walls of theapparatus, the invention provides an aerosol flow control apparatus,useful for either MDI or DPI devices, including a housing defining aconduit, the conduit having an open end defining a mouthpiece and asubstantially closed end defined by an end wall remote from themouthpiece, with a medication dispenser assembly being arranged withinthe housing to direct medication into the conduit. The medicationdispenser may be a pressurized canister with actuator and nozzle, oralternatively may be a dispenser for a medication in dry powder form.The end wall includes a plurality of auxiliary air inlets in fluidcommunication with ambient air outside the conduit, the auxiliary airinlets opening into the conduit adjacent the inner wall of the conduit,in a direction generally toward the open end of the mouthpiece. Theconduit further includes a plurality of vortex generators mounted on theinner wall thereof downstream of the auxiliary air inlets, the auxiliaryair inlets and vortex generators cooperating to establish a turbulentairflow along the inner wall of the conduit upon an inspiratory effortbeing exerted on the mouthpiece. The auxiliary air flow acts as a bufferor boundary layer flow along the inner walls of the conduit, reducingthe liklihood of aerosol droplets or dry particles impacting andpermanently sticking to the inner walls. The vortex generatorspreferably comprise inwardly directed vanes which are oriented at anangle to the axial direction so as to impart swirl and vorticity to theair flowing over them.

The invention further provides an aerosol flow control apparatus for usewith a pressurized canister of medication, in which discharge of theaerosol plume is caused by the patient's inspiratory effort, with thetiming of the discharge in relation to the inhalation being selectivelyvariable. To these ends, the apparatus includes a housing adapted tosupport the canister between a first position in which the dischargestem of the canister is in an inoperative position to a second positionin which the discharge stem is in an operative position for discharginga metered volume of medication, the housing further including an outletthrough which a user can inhale, the outlet defining a primary airpassage. A canister restraint is arranged in the housing and is movablefrom a rest position in which relative movement between the canisterbody and discharge stem is prevented to a discharge position in whichsuch movement is permitted. The canister restraint forms a part of, oralternatively is attached to, a device such as a bellows or a movablediaphragm piston assembly which defines a variable-volume chamber. Theinhaler includes a resilient member which urges the canister into thesecond position upon movement of the canister restraint into itsdischarge position. A secondary air passage extends through the housingbetween the primary air passage and ambient air outside the housing, thesecondary air passage including a venturi. The variable-volume chamberis in fluid communication with a throat of the venturi, wherebyinhalation of a user through the outlet causes a low pressure in theventuri throat so as to evacuate air from the chamber and thereby causethe canister restraint to move into the discharge position. Byappropriate selection of design parameters such as the chambercross-sectional area, the force exerted by the resilient member on thecanister, the venturi size, and the secondary air passage diameter, thedevice can be designed to cause actuation of the canister near the peakof a patient's inspiratory effort.

The device preferably further includes means for selectively varying thetiming of actuation. For instance, the device may include an adjustmentscrew intruding into the secondary air passage to act as a variable flowrestriction. Turning the screw one direction increases the amount offlow restriction, such that for a given inspiratory rate through themouthpiece, the amount of time required to evacuate the chambersufficiently to cause actuation is increased. Conversely, turning thescrew in the opposite direction decreases the amount of time required tocause actuation.

These and other objects and advantages of the present invention shallbecome more apparent from the accompanying drawings and the descriptionthereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various embodiments of theinvention and, together with the general description of the inventiongiven above and the detailed description given below, serve to explainthe principles of the invention.

FIG. 1 is a perspective view of an inhaler in accordance with theprinciples of the present invention.

FIG. 2 is an exploded view of the inhaler of FIG. 1.

FIG. 3 is a cross-sectional view of the inhaler taken along lines 3--3of FIG. 1.

FIG. 3A is a partial cross-sectional view showing an alternativeembodiment of the actuator and nozzle of the inhaler.

FIG. 4 is a cross-sectional view similar to FIG. 3, showing analternative embodiment of the inhaler.

FIG. 5 is a cross-sectional view similar to FIG. 3, showing yet anotheralternative embodiment of the inhaler.

FIG. 6 is cross-sectional view of the inhaler of FIG. 5 taken on a planenormal to that of FIG. 5.

FIG. 7 is a cross-sectional view of still another alternative embodimentof the invention, having features for achieving automatic actuation of acanister responsive to a patient's inhalation through the inhaler.

FIG. 8 is a perspective view of the trigger which engages and disengagesthe canister in the inhaler of FIG. 7.

FIG. 9 is side elevational view, partly in cross-section, of yet anotherembodiment of the invention, showing an alternative arrangement forachieving automatic actuation of a canister responsive to a patient'sbreath.

DETAILED DESCRIPTION OF THE DRAWINGS

FIGS. 1-3 depict a first embodiment of an inhaler 10 in accordance withthe principles of the invention. The inhaler 10 includes a housing 12which has a receptacle portion 14 connected to a conduit 16. Thereceptacle portion 14 is in the form of a sleeve adapted to receive astandard pressurized canister 18 containing a medication. The canister18 forms no part of the present invention. The inhaler apparatus of thepresent invention is usable with any standard pressurized canisterhaving an internal metering valve with a hollow discharge stem which maybe depressed inwardly with respect to the canister body from aninoperative position in which discharge of medications is prevented, toan operative position in which a metered volume of the canister contentsis discharged through the hollow discharge stem.

The conduit 16 includes an open end 20 spaced from the receptacleportion 14, and a closed end 22 defined by an end wall 24 which isconnected to the receptacle portion 14. The end wall 24 preferably isgenerally conical or hemispherical in shape, with an apex of the endwall 24 forming the portion of the end wall 24 farthest from the openend 20.

With reference to FIG. 3, the housing 12 further includes an actuatorand nozzle assembly 26 supported by the end wall 24. The actuator andnozzle assembly 26 includes a bore 28 which is adapted to receive thehollow discharge stem (not shown in FIGS. 1-3) of the canister 18, and anozzle discharge orifice 30 in fluid communication with the bore 28. Thenozzle discharge orifice 30 is advantageously located at the apex of theend wall 24 and oriented to direct an aerosol plume generally along thecentral longitudinal axis 32 of the conduit. The orifice 30 preferablyhas an internal diameter at the exit of less than about 0.025 inch, andmore preferably between about 0.005 inch and about 0.019 inch.

Thus, upon the canister 18 being depressed in the downward direction inFIG. 1, a metered volume of medication will be discharged into the bore28 and out the orifice 30 to form a generally conical plume ofaerosolized medication within the conduit 16, directed generally towardthe open end 20 thereof. The inhaler 10 includes features which promotedispersion and mixing of the aerosolized medication with air within theconduit to enhance evaporation and decrease the velocity of the liquidpropellant discharged from the canister 18. More specifically, theinhaler 10 includes an air tube 34 supported within the conduit 16. Theair tube 34 has an outlet 36 which is spaced downstream of and inopposing relationship with the nozzle discharge orifice 30, and an inlet38 which is in fluid communication with ambient air outside the conduit16. In the embodiment shown in FIGS. 1-3, the air tube 34 is a bent tubewhich has a generally axial portion 40 which is generally aligned alongthe conduit's longitudinal axis 32, and a generally radial portion 42which is attached to the inner wall 44 of the conduit 16. When a userexerts an inspiratory effort on the open end 20 of the conduit 16, airis drawn from outside the conduit 16 into the air tube inlet 38, exitingthe air tube outlet 36 in a direction toward the nozzle dischargeorifice 30. The portion 40 of air tube 34 is located and oriented withinthe conduit 16 so that air flowing out from the outlet 36 will impingeon a plume of aerosol exiting the nozzle orifice 30. Once this air flowfrom the tube 34 has been established, the metering valve of thecanister 18 is actuated to discharge a plume of aerosolized medicationfrom the orifice 30. The impingement of air from air tube 34 on theplume causes the plume to slow down and be dispersed so as to occupy alarger portion of the cross section of the conduit 16. The result isenhanced mixing of the aerosol with air, which promotes more completeevaporation of liquid propellant by the time the aerosol bolus exits heopen end 20 of the conduit 16, and a reduction in velocity of the plumeexiting the open end 20 so that it approaches the velocity of theinspiratory breath. Accordingly, a greater fraction of the metered doesof medication dispensed from the cansister 18 exits the open end 20 inthe form of respirable dry particles of the optimum size of about one tofive microns moving at a relatively low velocity that substantiallymatches the inspiratory breath velocity, as opposed to relatively largeliquid droplets moving at a relatively high velocity. Impaction andsticking of medication within the mouth and throat are thereby reduced.

The air tube 34 and conduit 16 can be integrally formed of one piece,with the internal passage of the air tube 34 extending through theconduit 16 to establish fluid communication with air outside the conduit16. Alternatively, the air tube 34 can be formed of a metal tube bentinto the appropriate configuration and attached to the conduit 16 at theinlet end 38.

Although the embodiments illustrated in FIGS. 1-3 and 7 show the airtube 34 bent at an angle of 90 degrees with the portion 40 coaxiallyaligned with the axis 41 (FIG. 3) of the nozzle orifice 30, otherarrangements may be used without sacrificing the advantages of theinvention. For example, the portion 40 may be arranged at an obtuseangle (i.e., between about 90 degrees and 180 degrees, 180 degrees beingdefined as exactly opposite to the direction of a plume exiting theorifice 30) to the axis 41 of the nozzle orifice 30, with the portion 40of air tube 34 being oriented to direct an air jet at the orifice 30.Additionally, the portion 42 which attaches to the conduit wall need notbe radial, but can be oriented at an acute or obtuse angle to theconduit wall 44.

The invention further includes features which reduce the likelihood ofliquid droplets or dry particles impacting and permanently sticking tothe inner walls 24 and 44 of the conduit 16. More particularly, theinhaler 10 includes a plurality of auxiliary air inlets 46 through theend wall 24 and circumferentially spaced therearound at at least twodifferent radii from the nozzle orifice 30. A first circumferential ringof auxiliary air inlets 46 are located adjacent the juncture 48 betweenthe end wall 24 and the inner wall 44 of the conduit 16. A secondcircumferential ring of auxiliary air inlets 47 are located radiallybetween the juncture 48 and the nozzle orifice 30. An inspiratory effortexerted on the open end 20 of the conduit 16 causes air to flow into theauxiliary air inlets 46 and 47 as indicated by arrows 50, and outwardtherefrom along the inner wall 44 of the conduit 16 and outward from endwall 24, as indicated by arrows 52. This auxiliary air flow forms abuffer or boundary layer air flow along the inner wall 44 and end wall24 which tends to reduce the impaction and permanent sticking ofmediation on inner wall 44 and end wall 24.

To the further attainment of this end, the inhaler 10 also includes aplurality of vortex generators or vanes 54 (best seen in FIG. 2) mountedon the inner wall 44 of the conduit 16 and extending inwardly therefrom.The vanes 54 are located downstream of the auxiliary air inlets 46, witheach vane 54 advantageously being located approximately in axialalignment with one of the auxiliary air inlets 46. The vanes 54 areoriented at an angle to the axial direction defined by longitudinal axis32, so that vorticity and swirl are imparted to air flowing over them.Thus, the boundary layer air flow created by auxiliary air inlets 46encounters the vanes 54, which impart vorticity and swirl to theboundary layer air flow. This vorticity and swirl further reduce thelikelihood of aerosol droplets or particles impacting and permanentlysticking to the inner wall 44.

As shown in FIGS. 1 and 3, the inhaler 10 includes a separate mouthpiece56 which connects to the open end 20 of the conduit 16. The mouthpiece56 has a reduced diameter portion 58 adapted to be inserted into themouth of a user of the inhaler 10. After completely exhaling, the userinserts the portion 58 into the mouth with the lips closed around theportion 58, and then begins to inhale, which establishes air flow fromthe air tube 34 and through the auxiliary air inlets 46. Once theseairflows are established and while continuing to inhale, the userdepresses the canister 18 to discharge a metered volume of medicationand propellant mixture from the nozzle discharge orifice 30. The usercontinues to inhale to fill the lungs to their capacity, and thentypically holds the breath for a period of time to allow the aerosolizedmedication to settle within the airways of the lungs.

As shown in FIGS. 1-3, the housing 12 is formed in four sections(including the mouthpiece 56) which telescopingly fit together. However,for ease of manufacturing, the housing 12 may alternatively be formed infewer than four sections. For example, the housing 12 may be formed intwo sections, a first section including the receptacle portion 14, endwall 24, and the conduit 16 up to and including the vanes 54, and asecond section including the portion of conduit 16 having the air tube34 and the mouthpiece 56. Alternatively, the housing 14 may be formed intwo sections split on a longitudinal plane through the conduit, the twosections being generally mirror images of each other which are joinedtogether along the plane of symmetry. Nevertheless, for illustrationpurposes, an embodiment having four sections is shown and described.

A first section 60 includes the receptacle portion 14, the end wall 24and actuator and nozzle assembly 26, and a generally cylindrical portion62 which forms a part of the conduit 16 and is connected to the end wall24 at the juncture 48. The first section 60 advantageously is integrallyformed of one piece, although it may alternatively be formed in multiplepieces which are subsequently joined together.

A second section 64 includes a second generally cylindrical portion 66whose inner and outer diameters are equal to those of the firstgenerally cylindrical portion 62, and a reduced-diameter portion 68which is telescopingly received within the downstream open end of firstcylindrical portion 62. The portion 68 has an inner wall 70 which isgenerally conical, converging slightly in the axial direction toward themouthpiece 56. The vanes 54 are mounted on the inner wall 70. Secondsection 64 preferably is integrally formed on one piece, although it mayalternatively be formed in multiple pieces which are subsequentlyjoined.

A third section 72 of the housing 12 includes a third generallycylindrical portion 74 whose inner and outer diameters are equal tothose of the second generally cylindrical portion 66, and a reduceddiameter cylindrical portion 76 which is telescopingly received withinthe open downstream end of second generally cylindrical portion 66. Theouter diameter of portion 76 is approximately equal to the innerdiameter of portion 66 so as to provide a tight fit between those parts.The inner surface 78 of portion 76 has a diameter which is approximatelyequal to the smallest diameter of the conical inner wall 70 so that thejuncture between surfaces 70 and 78 does not present any substantialstep in the flowpath defined by the conduit 16. The air tube 34 ismounted on the inner surface of the third section 72 at the juncturebetween the inner surface 78 and the inner surface 80 of thirdcylindrical portion 74. A hole 82 through the portion 74 mates with theinternal passage of air tube 34 to provide fluid communication betweenthe inlet 38 of air tube 34 and ambient air outside the conduit 16.Third section 72 may be integrally formed of one piece or formed inmultiple pieces and subsequently joined.

The fourth section of the housing 12 is the mouthpiece 56, which has agenerally cylindrical portion 84 which is telescopingly received withinthe open downstream end of the third generally cylindrical portion 74(which also defines the open end 20 of the conduit 16). The portion 84is attached to an annular flange 86, which in turn is attached to thereduced diameter portion 58 which is inserted into a user's mouth. Theouter diameter of portion 84 is approximately equal to the diameter ofinner surface 80 so as to provide a tight fit therebetween.

The housing 12 advantageously is formed of a plastic such as polyamide,polyester, polyproplene, polyethylene, ABS, polycarbonate, orpolyacrylate. The housing 12 may be manufactured by any suitabletechnique such as injection molding or blow molding.

FIG. 3A shows an alterative embodiment of an actuator and nozzleassembly 26a for the inhaler 10, in cross-sectional view on thehorizontal plane illustrated in FIG. 3. The actuator and nozzle assembly26a includes two spaced-apart discharge orifices 30a which are bothfluidly connected to the bore 28a and which converge toward each otherin the direction of the mouthpiece 56. Thus, depressing the canister 18so as to discharge a metered volume of medication into the bore 28acauses two aerosol plumes to be emitted from the pair of orifices 30a.The plumes converge and impinge on each other upstream of the air tubeoutlet 36, causing the aerosol to spread out, thereby aiding mixing ofthe aerosol with air. Additionally, impingement of the two plumes aidsin creating smaller droplets, which enhances evaporation of propellant.It will be appreciated that for convenience of illustration, the bore28a is shown as being elongated in the horizontal direction and orifices30a are shown as being spaced apart in the horizontal plane.Advantageously, however, the bore 28a may simply be extended in thevertical direction and the orifices 30a vertically spaced apart andangled toward each other so as to achieve the desired convergence of thetwo plumes.

FIG. 4 depicts an alternative embodiment of an inhaler 10a in which theelongated air tube 34 of inhaler 10 has been replaced by a shorter airtube in the form of a hub 40a which is supported in the conduit 16 by apair of hollow spokes 42a. In FIG. 4, parts identified by referencenumerals having the letter "a" suffix denote parts analogous to thosebearing the same reference numerals without the suffix in FIG. 3, whileparts identified with identical reference numbers in FIGS. 3 and 4denote identical parts. Thus, the hub 40a is analogous to the axialportion 40 of the air tube 34, and the spokes 42a are analogous to theradial portion 42 of air tube 34. The hub 40a includes a central cavity88 of a first diameter, and an outlet passage 36a of a second smallerdiameter. The outlet passage 36ais generally coaxial with the conduit 16and oriented so that air flowing outward therefrom is directed towardthe nozzle orifice 30. The internal passages of spokes 42a are connectedto outside air by a pair of holes 82a through the cylindrical portion74a. In the embodiment of the inhaler 10ashown in FIG. 4, there is nosection of the housing analogous to the second section 64 of FIG. 3.Thus, the vanes 54 have been eliminated from the inhaler 10a. However,the auxiliary air inlets 46 are still present in the inhaler 10a toprovide a boundary layer air flow along the inner wall of the conduit16a.

FIGS. 5 and 6 illustrate yet another embodiment of an inhaler inaccordance with the principles of the present invention. FIG. 5schematically depicts a horizontal cross section analogous to FIG. 3,showing an inhaler 10b in which the aerosol plume is directed away fromthe user so that the aerosol must reverse direction before beinginspired. FIG. 6 schematically depicts a vertical cross section of theinhaler 10b. Again, like parts are denoted by like reference numerals,while analogous parts are denoted by the letter "b" suffix. The inhaler10b includes a housing 12b defining a conduit 16b which has a firstclosed end defined by an end wall 90 and a second open end defined by amouthpiece portion 58b adapted to be inserted into a user's mouth. Theconduit 16b has a first larger internal cross sectional area over themajority of its length, narrowing to a second smaller internal crosssectional area at the mouthpiece portion 58b. The housing furtherincludes a receptacle portion 14b which penetrates into the conduit 16bat a location between the end wall 90 and the mouthpiece portion 58b.The receptacle portion 14b receives a standard pressurized canister (notshown). The housing 12b further includes an actuator and nozzle assembly26 arranged at the bottom end of receptacle portion 14b such that thehollow outlet stem of the canister may be inserted into a bore 28 of theactuator and nozzle assembly 26. The details of the actuator and nozzleassemble 26 have already been described in connection with FIG. 3. Thenozzle discharge orifice 30 is oriented so as to direct an aerosol plumetoward the end wall 90.

The inhaler 10b includes an internal conduit 92 which is coaxiallydisposed with the conduit 16b. The internal conduit 92 has an open end94 spaced from and adjacent the end wall 90, and a closed end 96 remotefrom the end wall 90 and defined by an end wall 24b which supports theactuator and nozzle assembly 26. The inhaler further includes an airtube 34b attached to the end wall 90 and coaxially disposed within theconduit 16b. The air tube 34b intrudes part way into the inner conduit92 toward the nozzle discharge orifice 30. The inlet 38b of air tube 34bis connected to ambient air outside the conduit 16b by a hole 98 throughend wall 90. The outlet 36b of air tube 34b is in opposing relation tothe orifice 30. Aerosol emitted from the orifice 30 enters into theinterior of inner conduit 92 and proceeds toward the end wall 90 ofouter conduit 16b. Inhalation of the user through the mouthpiece 58bcauses air to enter through hole 98 into air tube 34b and out the outlet36b toward the plume. The plume and the air jet from air tube 34b meet,causing the plume to slow down and spread out within inner conduit 92.Continued inhalation by the user causes the dispersed aerosol to exitthrough the open end 94 of inner conduit 92, and then reverse directionsto flow through the space between the inner conduit 92 and the outerconduit 16b, and thence through the mouthpiece 58b. Thus, the aerosoltravels a portion of the length of conduit 16b twice, thereby increasingresidence time of the aerosol within the device before exiting themouthpiece 58b. This leads to more complete evaporation of liquidpropellant. Furthermore, the flow reversal insures that the velocity ofthe aerosol exiting the mouthpiece will be substantially equal to thevelocity of the user's inspired breath, reducing the problem ofimpaction in the mouth and throat.

FIG. 7 depicts yet another embodiment of the invention providingautomatic actuation of the canister to discharge a dose of medication inresponse to, and synchronized with, the user's inspiratory effort. Aninhaler 10c includes a housing 12c having a conduit 16c within which anaerosol plume is created for inhalation by the user. The conduit 16c isshown to include the air tube 34 and the auxiliary air inlets 46. It mayalso include the vanes 54 of inhaler 10. Alternatively, the conduit 16cmay be a simple straight duct with an open end for the exit ofaerosolized medication. Thus, with the exception that the conduit 16cmust adapted to provide fluid communication with a chamber 162 inhousing 12c as discussed below, the details of the conduit 16c are notimportant to an understanding of the breath-synchronization features ofthe invention.

The housing 12c further includes a receptacle portion 14c which isconnected to the conduit 16c. The receptacle portion 14c comprises agenerally cylindrical sleeve having a longitudinal axis 108 which isoriented at an oblique angle to the longitudinal axis of the conduit16c. A canister 18 resides within the receptacle portion 14c with itslongitudinal axis aligned with the longitudinal axis of the receptacleportion 14c. Disposed between the receptacle portion 14c and thecanister 18 is an inner sleeve 100. The inner sleeve 100 has an open topend 102 through which the canister 18 may be inserted, and an openbottom end 104 which is restricted such that the canister 18 cannot gothrough it but which nevertheless permits the hollow stem 19 of thecanister to be inserted into the bore 28 of actuator and nozzle assembly26. More specifically, the sleeve 100 adjacent bottom end 104 hasinwardly extending ledges 105 which abut the cap portion 106 of thecanister. The canister 18 is slidable within inner sleeve along thedirection defined by the longitudinal axis 108 of receptacle portion 14cso as to permit the canister to be depressed toward the actuator andnozzle assembly 26 in order to actuate the canister's metering valve.

The inner sleeve 100 is also slidable within the receptacle portion 14calong the direction of axis 108 for the purpose of placing the canister18 in a cocked position ready to be actuated. The receptacle portion 14chas four longitudinal slots 110 circumferentially spaced apart about 90degrees, two of which receive a pair of diametrically opposite lugs orcam followers 112 extending outwardly from the outer surface of innersleeve 100. Alternatively, the receptacle portion 14c may have only twoslots 110 spaced 180 degrees apart and receiving the lugs 112. Thus, asthe inner sleeve slides longitudinally within receptacle portion 14c,the lugs 112 slide longitudinally within the respective slots 110.

The inhaler includes a generally cylindrical cam ring 114 which fitsover the outside of receptacle portion 14c. The cam ring 114 has anannular flange 116 at its lower end which extends outward beyond theouter surface of the housing so as to facilitate gripping of the camring 114 by the user's hand. The inner surface 118 of ring 114 has apair of circumferentially extending recesses or cam tracks 120 formedtherein approximately 180 degrees apart which extend longitudinallyupward to the open top end 122 of cam ring 114. Each cam track 120presents a generally helical surface 124 in facing relationship with oneof the lugs 112 protruding outwardly from the inner sleeve 100 throughslots 110. Thus, starting with the cam ring 114 in a position in whicheach lug 112 is in contact with the lowermost portion of the respectiveam track 120 (i.e., that portion of cam track 120 which is farthest fromthe top end 122 of cam ring 114), rotation of the cam ring 114 throughthe arc defined by the cam tracks 120 causes the lugs 112 to ride alongthe helical surfaces 124 and thereby upwardly advance the inner sleeve100 in the longitudinal direction toward the top end 122.

This upward movement of the inner sleeve 100 draws the canister 18upward by virtue of the ledges 105. Resisting this upward movement ofthe canister 18 is a compression spring 126. The spring 126 is attachedto the inner surface of a removable end cap 128 which surrounds the topend 130 of the receptacle portion 14c and the top end 122 of the camring 114 to completely enclose the canister 18 in the housing. When theend cap 128 is thus installed, the spring 126 bears against the end ofthe canister 18, biasing the canister downward toward the actuator andnozzle assembly 26. With nothing to impede the downward movement of thecanister 18, the spring 126 would move the canister downward until thedischarge stem 19 were fully depressed into the canister so as to causedischarge of a metered volume of the canister contents. However, theinhaler 10c includes a mechanism which engages the canister to preventthis downward movement, with the mechanism being responsive to aninspiratory effort of a user exerted on the open end of the conduit 16cso as to disengage from the canister during the user's inhalation toallow the spring 126 to move the canister into its discharge position.

To these ends, the inhaler 10c includes a piston assembly 132 which ismovable relative to the canister 18 along an axis 134 generally normalto the longitudinal axis 108. The piston assembly 132 includes acircular disc 136 having a shaft 138 extending centrally therethroughcoaxial with axis 134 and protruding outward from both sides of the disc136. A first portion 140 of the shaft 138 protruding from the side ofdisc 136 remote from the canister engages a recess 142 in a wall 144 ofthe housing, the recess 142 guiding the movement of the piston assembly132 along axis 134. A second portion 146 of shaft 138 protruding fromthe side of disc 136 facing the canister extends through an opening 148in receptacle portion 14c, terminating at an enlarged head end 150. Acompression spring 152 is captive between the head end 150 and the wallof the receptacle portion 14c, biasing the piston assembly 132 towardthe canister 18.

A forked trigger 154 is attached to the head end 150. The trigger 154has two spaced-apart parallel prongs 156 (FIG. 8) which extend along thedirection of axis 134 to approximately the longitudinal axis 108 of thereceptacle portion 14c. The prongs 156 are spaced apart by a distance Dwhich is slightly smaller than the diameter of the canister neck 158from which the discharge stem 19 protrudes, as shown schematically inFIG. 8. Thus, when the piston assembly 132 is fully extended toward thecanister 18, the canister neck 158 contacts inner edge portions 160 ofthe prong 156, as indicated by the shaded regions in FIG. 8. However,when the piston assembly 132 is withdrawn along axis 134 away from thecanister 18, the canister neck 158 clears the prongs 156 so thatmovement of the canister 18 toward the actuator 26 is permitted. Theprongs 156 include portions 157 which slope gently away from thecanister neck 158 in the direction along axis 134 toward the canister.The portions 157 reduce the amount of force required for disengagementof the trigger 154 from the canister neck 158.

Movement of the piston assembly 132 in the direction away from thecanister is responsive to air pressure within a variable-volume chamber162 within the housing. The chamber 162 is defined by the disc 136, thehousing wall 144, and a flexible diaphragm 164 which connects the disc136 to the wall 144 in a substantially air-tight manner. Advantageously,the diaphragm 164 includes a circular portion 166 which lies against theside of disc 136 facing the canister 18, and a skirt 168 which dependsfrom the outer edge of the circular portion 166 and attaches to thehousing wall 144. Further advantageously, the housing wall 144 comprisesa removable cover 170 of the housing, and an edge of the skirt 168 isattached to the housing by being sandwiched between the cover 170 andthe remainder of the housing. The circular portion 166 of diaphragm 164includes a central hole through which the shaft 138 extends and whichtightly surrounds the shaft 138 to provide a substantially air-tightseal therebetween.

The removable cover 170 includes a recess 172 facing the disc 136 whichaligns with a passage 174 formed in a sidewall 176 of the housing. Thepassage 174 extends toward the open end 20c of conduit 16c. The conduit16c is formed in at least two sections, a first generally cylindricalsection 62c which includes the sidewall 176 and is connected to the endwall 24c through which the nozzle orifice 30 extends, and a secondgenerally cylindrical section 74c which includes the air tube 34 andwhich connects to the first section 62c. The passage 174 terminates atthe end of first section 62c which connects to second section 74c. Apassage 178 through a sidewall 180 of the second section 74c is fluidlyconnected with and forms an extension of passage 174. The passage 178extends into the internal passage 182 of the air tube 34. A venturi 184is inserted into the air tube passage 182. The venturi 184 includes arestricted portion or throat 186. Air passages 188 extend through theventuri wall in the vicinity of the throat 186. The venturi 184 isdisposed in passage 182 such that these air passages 188 align with thepassage 178. Thus, fluid communication is provided between the venturithroat 186 and the variable-volume chamber 162 by air passages 188,passage 178 in second section 74c, passage 174 in first section 62c, andrecess 172 in cover 170.

It will therefore be appreciated that when a user inhales through theopen end 20c of conduit 16c, air is drawn from outside the conduit 16cthrough air tube 34 into the primary air passage of the conduit 16c.This air has to flow through the venturi 184, and consequently abelow-atmospheric air pressure exists in the venturi throat 186. Thisbelow-atmospheric air pressure is communicated to the chamber 162, withthe result that the walls of the chamber 162 are subjected to a forceproportional to the pressure difference between atmospheric pressureoutside the chamber 162 and the below-atmospheric pressure inside thechamber 162. Consequently, air within the chamber 162 begins to evacuatethe chamber 162 through recess 172, through passages 174 and 178,through passages 188, and into the venturi throat 186, and thencethrough the air tube 34 into the primary air passage of the conduit 16c.

As the user continues to inhale through the conduit 16c, evacuation ofair from the chamber 162 causes the volume in chamber 162 to decrease,with the result that the disc 136 and the shaft 138 begin to move towardthe wall 144 against the force of the spring 152. Accordingly, thetrigger 154 begins to move so as to disengage the prongs 156 from thecanister neck 158. When the decrease in volume is sufficient to move thetrigger 154 far enough to totally disengage the prongs 156 from the neck158, movement of the canister 18 toward the actuator 26 is no longerimpeded, and the force of spring 126 moves the canister downward so asto cause actuation of the canister's metering valve. A metered dose ofaerosolized medication is thereby discharged from nozzle orifice 30 intothe conduit 16c for inhalation by the user.

After the inhaler 10c has been actuated to dispense a dose ofmedication, it must be recocked so that it is ready to be dischargedagain. To this end, the user grasps the ring 114 and rotates it withrespect to the housing 12c through the arc defined by the cam racks 120.This causes the inner sleeve 100 and canister 18 to be lifted upwardagainst the force of spring 126. When the canister 18 is raised upwardlysufficiently to allow the trigger 154 to clear the canister neck 158,the spring 152 urges the trigger 154 toward the canister 18 so that thetrigger 154 once again is in a fully extended position to engage thecanister neck 158. The user then rotates the cam ring 114 back to itsstarting position to lower the canister 18, whereupon the canister neck158 seats against the prongs 156 of the trigger 154. The inhaler 10c isthen ready to be used again.

It will be appreciated that the breath-synchronization featuresdescribed above provide an inhaler in which discharge of medication isautomatically responsive to the user's inspiratory effort, so that theuser does not have to carefully coordinate manual depression of acanister with the inhalation. Furthermore, discharge of medication doesnot occur immediately upon the user beginning to inhale on the open endof the device, but rather is somewhat delayed until the volume ofchamber 162 has decreased enough to cause actuation. It will also beappreciated that the degree of time delay between initiation of a breathand actuation is dependent on a number of factors, the primary factorsbeing the cross-sectional area of the chamber 162 and the springconstant of the spring 152, since a discharge of medication requires acertain minimum travel of the canister 18 to cause the discharge stem 19to be fully depressed, and the travel is proportional to the pressuredifference across the chamber times its cross-sectional area divided bythe spring constant. Accordingly, the inhaler 10c may be designed withappropriate selection of these factors so as to achieve actuation of thecanister 18 near the peak of a user's inhalation.

Moreover, the inhaler 10c provides breath-responsive actuation of thecanister 18 which automatically adjusts to the user's rate of inhalationto discharge the medication near the peak of the inhalation, i.e., nearthe point at which 50 percent of the volume which the user willeventually inspire with a full inhalation has been inspired. Forinstance, if a user with normal lung function inhales quickly throughthe open end 20c, air will be evacuated from the chamber 162 morerapidly so as to achieve actuation in a relatively short time.Conversely, if a user with impaired lung function inhales slowly throughthe open end 20c, air will be evacuated more slowly from chamber 162 soas to achieve actuation in a relatively longer time.

The inhaler 10c further includes an adjustment screw 190 which extendsthrough the housing 12c into the passage 174 to form a restrictionwithin passage 174. By turning the screw 190 one direction, the screw190 extends farther into passage 174 to increase the restriction, and byturning the screw 190 the opposite direction, it retracts to decreasethe restriction. Thus, the timing of actuation of the canister 18 inrelation to a particular patient's inhalation may be varied by adjustingthe screw 190. Varying the screw position results in a variation inpressure difference across the walls of the variable-volume chamber 162at a given flow rate out the open end 20c of conduit 16c. Thus, for agiven flow rate out the open end 20c of conduit 16c, turning the screw190 to increase the restriction of passage 174 will increase the timeperiod required to evacuate the chamber 162 sufficiently to causeactuation, whereas turning the screw 190 to decrease the restrictionwill decrease such time period.

FIG. 9 depicts a subassembly of yet another embodiment of an inhalerhaving features for automatic breath actuation of discharge. In thisembodiment, the forked trigger 154 is eliminated and the diaphragmpiston assembly 132 is replaced by a resiliently compressible bellows200 which is disposed between a fixed wall of the housing (not shown)and the canister neck 158. The bellows 200 itself acts as the restraintwhich keeps the canister in a non-actuated position, the bellows beingcompressed by air pressure into a position permitting the canister tomove into a discharge position.

The bellows 200 is advantageously made of stainless steel and has ablind end wall 204 at the end adjacent the canister neck 158, the endwall 204 being integrally formed with the accordion-folded side wall206. The bellows 200 has a second end wall 208 at the end adjacent thehousing wall 202, the end wall 208 also being integrally formed with theside wall 206. The second end wall 208 is pierced by a tube or needle210 which establishes an air passage into the interior of the bellows200. The needle 210 advantageously is a stainless steel tube similar toa hypodermic needle and is integrally affixed at one end to the end wall208 by welding or other suitable technique. The free end 212 of theneedle 210 extends is attached via an extension tube 213 to the throat214 of a venturi 216. The venturi 216 is disposed within a tube 218which extends from an inlet end 220 which draws air from outside theinhaler housing, to an exit end 222 which is arranged within the conduit(not shown) opposite the nozzle discharge orifice 30. The tube 218 andventuri 216 may also be formed of stainless steel.

A support/release platform 224 is attached to the blind end wall 204 ofthe bellows 200. The support/release platform 224 contacts the canisterneck 158 throughout the range of motion undergone by the canister inmoving from a rest or ready position to a discharge position. Thebellows 200, via the support/release platform 224, exerts a spring forceon the canister neck 158. The force of the bellows 200 acts in adirection tending to move the canister neck 158 away from the actuator26. Additionally, as is well known, the canister 18 contains an internalspring (not shown) which acts between the canister body and the hollowoutlet stem 19 in a direction tending to move the canister 18 away fromthe actuator 26. The spring constant of the bellows 200 is selected suchthat the sum of the spring force exerted by the bellows 200 and theforce exerted by the internal spring is slightly greater than the forceexerted by the spring 126 (FIG. 7) which exerts a force on the end ofthe canister 18 in the direction to tend to move the canister 18 towardthe actuator 26 into its discharge position. Thus, at rest, withatmospheric pressure acting both inside and outside the bellows 200, thebellows 200 and internal spring overcome the force of the spring 126 andthereby keep the canister 18 in a ready position preventing discharge ofmedication therefrom.

However, when a user inhales through the outlet (not shown) of theinhaler, air is drawn through the tube 218, as previously described inconnection with the inhaler 10c, which creates a low pressure within thethroat 214 of venturi 216. This low pressure is communicated via theextension tube 213 and needle 210 to the interior of the bellows 200. Asa result, the pressure within the bellows 200 is less than theatmospheric pressure which surrounds the outside of the bellows 200, andtherefore there is an air pressure force exerted on the blind end wall204 in the direction toward the housing wall 202. The sum of this airpressure force and the force of the spring 126 exceed the spring forcesexerted by the bellows 200 and the canister internal spring, causing theblind end wall 204 of bellows 200 to be compressed toward the housingwall 202. By virtue of the force exerted on the canister 18 by thespring 126, the canister follows the end wall 204. With continuedevacuation of air from the bellows 200, the canister 18 is moved intoits discharge position. Once the user completes his inhalation and airflow through the venturi 216 ceases, air pressure is again equalizedinside and outside the bellows 200, and the bellows 200 returns to itsstarting position, the forces of the bellows 200 and internal springforcing the canister 18 back upward against the force of the spring 126into the ready position. Thus, with the breath-actuation system depictedin FIG. 9, there is no need for a separate cocking system.

The bellows 200 preferably has a spring constant of about 1 pound perinch to about 12 pounds per inch, and a cross-sectional area of about0.2 to about 0.75 square inch. Thus, a pressure differential of aboutone pound per square inch across the bellows 200 is sufficient tocompress the bellows 200 by an amount of about 0.010 inch to about 0.080inch. With a standard canister 18, only about 0.010 inch of relativemovement is required between the discharge stem 19 and the canister bodyin order to cause discharge. Accordingly, the venturi 216 must be sizedto create a gage pressure within the throat 214 of about one pound persquare inch.

While the present invention has been illustrated by a description ofvarious embodiments and while these embodiments have been described inconsiderable detail, it is not the intention of the applicants torestrict or in any way limit the scope of the appended claims to suchdetail. Additional advantages and modifications will readily appear tothose skilled in the art. For example, while the inhalers which areillustrated and described have the venturi inlet in communication withambient air via a passage through the conduit wall, the venturi inletmay alternatively draw air through one of the auxiliary air inlets 46 inthe end wall 24, or through any arrangement having the venturi inletoutside the primary air passage defined by the inhaler conduit.Additionally, the stainless steel bellows 200 of FIG. 8 mayadvantageously be used in the inhaler configuration depicted in FIG. 7,with the bellows 200 replacing the piston assembly 132 and the blind endwall 204 of the bellows 200 being attached to the forked trigger 154,and the spring 152 being eliminated by virtue of the resiliency of thebellows 200. The invention in its broader aspects is therefore notlimited to the specific details, representative apparatus and methods,and illustrative examples shown and described. Accordingly, departuresmay be made from such details without departing from the spirit or scopeof applicant's general inventive concept.

What is claimed is:
 1. An aerosol flow control apparatus providingautomatic discharge of medication responsive to an inspiratory effort ofa user, the apparatus comprising:a pressurized canister of medicationincluding a canister body and a hollow discharge stem which is movablewith respect to the canister body between an inoperative position inwhich discharge of medication is prevented and an operative position inwhich medication is discharged through the discharge stem; a housingadapted to support the canister and permit movement thereof between afirst position in which the discharge stem is in the inoperativeposition to a second position in which the discharge stem is in theoperative position, the housing further defining a primary air passageincluding an outlet through which a user can inhale and also defining asecondary air passage extending between the primary air passage andambient air outside the primary air passage, the secondary air passageincluding a venturi having a throat; a variable-volume device supportedwithin the housing and including a wall which is movable with respect tothe housing, the variable-volume device defining a variable-volumechamber therein in fluid communication with the venturi throat; acanister restraint affixed to the movable wall of the variable-volumedevice, the canister restraint being movable with the movable wall froma rest position in which the canister is in the first position andrelative movement between the canister body and discharge stem isprevented, to a discharge position in which the canister is free to moveinto the second position; a resilient member which urges the canisterinto the second position upon movement of the canister restraint intoits discharge position; and the variable-volume chamber being in fluidcommunication with the primary air passage, whereby inhalation of a userthrough the outlet causes air to be drawn through the venturi throatthereby creating a low pressure in the throat which is communicated tothe variable-volume chamber, the low pressure causing air to beevacuated from the chamber and thereby cause the movable wall to movethe canister restraint into the discharge position.
 2. The aerosol flowcontrol apparatus of claim 1, wherein the venturi throat is connected tothe chamber by a third air passage within the housing, and furthercomprising an adjustment device which may be selectively positioned toselectively vary the flow rate through the third air passage at a givenflow rate through the primary air passage, thereby varying the timing ofmedication discharge in relation to the inhalation cycle of a user. 3.The aerosol flow control apparatus of claim 1, wherein thevariable-volume device comprises a piston which is sealingly connectedto a wall of the housing by a flexible diaphragm, and the canisterrestraint includes a member which is attached to the piston and which inthe rest position intrudes into the path traveled by the canisterbetween the first and second positions so as to prevent the canisterfrom moving into the second position, evacuation of air from within thechamber of the variable-volume device causing the piston to move towardthe housing wall and thereby withdraw the member into the dischargeposition permitting the canister to move into the second position. 4.The aerosol flow control apparatus of claim 1, wherein the housingcomprises a main body portion which receives the canister, and an endcap which covers the end of the canister opposite from the end with thedischarge stem and which engages the main body portion to preventinadvertent removal therefrom, the resilient member comprising acompression spring between an inner surface of the end cap and thecanister such that the spring bears against the canister when the endcap is engaged with the main body portion.
 5. The aerosol flow controlapparatus of claim 3, wherein the main body portion includes a generallycylindrical receptacle having a longitudinal axis and defining agenerally cylindrical recess in which the canister resides, and furthercomprising a cocking device including:an inner sleeve which surroundsthe canister within the receptacle, the inner sleeve and canister beingslidable together as a unit within the receptacle along the longitudinalaxis, the inner sleeve further including at least one pin extendingoutwardly from an outer surface thereof through a slot in thereceptacle; and a cocking ring which surrounds the receptacle and has asurface which engages the at least one pin, the cocking ring beingmovable with respect to the receptacle so as to move the pin in thedirection defined by the longitudinal axis toward the end cap so as todraw the inner sleeve and canister upward and thereby move the canisterinto a cocked position which permits the canister restraint to move intoits rest position, thereby readying the apparatus for actuation inresponse to the inspiratory effort of a user.
 6. The aerosol flowcontrol apparatus of claim 1, wherein the variable-volume devicecomprises a resiliently compressible bellows, the bellows being disposedbetween a neck of the canister and a wall of the housing which faces thecanister neck, the movable wall being an end wall of the bellows, thecanister restraint being affixed to the end wall and contacting thecanister neck, the bellows being compressible toward the housing wall ina direction substantially parallel to the direction in which thecanister moves from the first position to the second position, thebellows being adapted to exert a spring force on the canister tending tourge the canister toward the first position, the spring force exceedingthe force exerted on the canister by the resilient member by apredetermined amount which is selected such that when a user inhalesthrough the outlet of the housing, the pressure force exerted on the endwall of the bellows by the difference between atmospheric pressureoutside the bellows and the low pressure inside the bellows exceeds thepredetermined amount, thereby causing the end wall to compress thebellows toward the housing wall and move the canister restraint into thedischarge position such that the canister is moved into the secondposition by the resilient member.
 7. In an aerosol delivery apparatuswhich houses a medication-containing canister having a canister body anda hollow outlet stem movable with respect to the canister body betweenan inoperative position in which discharge of medication is preventedand an operative position in which medication is discharged through theoutlet stem, with the canister being movable within the apparatusbetween a first position in which the outlet stem is in the inoperativeposition and a second position in which the outlet stem is in theoperative position, the apparatus including a housing defining a primaryair passage having an outlet through which a user can inhale, a methodof synchronizing discharge of medication from the canister with aninspiratory effort of a user through the outlet, the methodcomprising:placing the canister in the first position; preventingmovement of the canister into the second position by a canisterrestraint which engages the canister to prevent said movement and whichis movable in response to below-atmospheric air pressure within avariable-volume device arranged within the housing, the variable-volumedevice defining an air chamber therein, the canister restraint beingmovable to permit the canister to move into the second position upon apredetermined decrease in volume of the air chamber; urging the canistertoward the second position; upon a user inhaling through the outlet,drawing air through a secondary air passage arranged within the housing,the secondary air passage extending from the primary air passage toambient air outside the primary air passage; and at least during thedrawing step, providing fluid communication between the secondary airpassage and the air chamber so as to communicate a below-atmospheric airpressure to the air chamber and thereby cause the chamber volume todecrease, whereby the canister restraint moves to permit said movementof the canister into the second position to discharge medication whenthe predetermined decrease in chamber volume is reached.
 8. The methodof claim 7, wherein the providing step comprises providing fluidcommunication between a throat portion of the secondary air passage andthe variable-volume chamber to evacuate air therefrom, the throatportion having a reduced cross-sectional flow area relative to theremainder of the secondary air passage such that the air pressure in thethroat portion is lower than the air pressure in the remainder of thesecondary air passage when air is flowing therethrough.